Relationship between prognostic score and thyrotropin receptor (TSH-R) in papillary thyroid carcinoma: immunohistochemical detection of TSH-R

Tanaka, Katsuhiro; Inoue, Hiroyuki; Miki, Hitoshi; Masuda, Eitarou; Kitaichi, Masanori; Komaki, Kansei; Uyama, Tadashi; Monden, Yasumasa

doi:10.1038/bjc.1997.431

Cited by 31 publications

(22 citation statements)

References 20 publications

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“…Futhermore, in agreement with another previous finding (6), we demonstrated that the poorlydifferentiated components, such as trabecular, solid and insular ones, had decreased TSHR expression in most of the PDC cases. A previous study reported that clinically high-risk patients with PTC tended to show weaker TSHR staining than that of normal thyroid of the same patients (16). However, in the present study we found that the PTC cases did not show weaker staining than the PDC cases, which may indicate that the decline of TSHR expression affects the biological behavior of thyroid carcinomas.…”

Section: ------------------------------------------------------------contrasting

confidence: 57%

“…Certain authors have reported TSHR localized along the basal surface (14), while others reported it in the cytoplasm (16). Although we examined another antibody used in the previous reports (6,14,16), there is no remarkable difference between these two antibodies. To confirm the antibody specificity, Western blotting was performed using normal thyroid tissue.…”

Section: Discussionmentioning

confidence: 99%

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Decreased expression of the thyroid-stimulating hormone receptor in poorly-differentiated carcinoma of the thyroid

Matsumoto

Sakamoto²,

Fujiwara³

et al. 2008

Oncol Rep

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Abstract. Poorly-differentiated carcinomas (PDCs) occupy an intermediate position between differentiated (follicular and papillary) and undifferentiated carcinomas (UDCs) based on morphology and behavior. However, its definition remains unclear, especially in the differentiation of thyroid function. To characterize the hormonal differentiation of PDCs, in addition to the morphological definition, we immunohistochemically investigated the thyroid-stimulating hormone receptor (TSHR) and thyroid transcription factor 1 (TTF-1) as regulators of thyroid hormonal function and differentiation. We comparatively studied their expression in 15 papillary carcinoma (PTC), 8 PDC and 8 UDC cases and further analyzed their correlation to proliferation activity as estimated by the MIB-1 index. All cases of PTC and PDC expressed the TSHR, whereas all cases of UDC did not. Notably, most of the PDCs showed more decreased and heterogeneous expression in the poorly-differentiated component than in the welldifferentiated one within the same case. Examining the heterogeneous areas in PDC, we found an inverse relationship between TSHR expression and the MIB-1 index, that is, decreased TSHR expression was correlated to high proliferation. Unexpectedly, TTF-1 expression was observed in almost all of the PTC and PDC cases and in half of the UDC cases; therefore, it was not useful to distinguish PDC from PTC or UDC. In conclusion, we demonstrated that TSHR expression was decreased in PDCs despite conserved TTF-1 expression and that it correlated to the proliferative activity in PDCs.

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Section: ------------------------------------------------------------contrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Decreased expression of the thyroid-stimulating hormone receptor in poorly-differentiated carcinoma of the thyroid

Matsumoto

Sakamoto²,

Fujiwara³

et al. 2008

Oncol Rep

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“…Ao contrário, no trabalho feito por Tanaka e cols. (24), observou-se que a expressão de TSHR2 seria menor nas variantes de pior prognóstico, porém, deixando claro que essa menor expressão seria concluída levando-se em conta a coloração heterogênea de diferentes áreas dentro do tumor, fato este não levado em consideração neste estudo.…”

Section: Variantes De Prognóstico Intermediáriounclassified

“…Há relação inversa entre o nível de receptor de TSH e a agressividade de carcinomas de tiróide (23). Os carcinomas papilíferos com baixa expressão de receptor de TSH possuem tendência para serem encontrados em estágios avança-dos e estão associados com pior prognóstico (24).…”

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Caracterização molecular das variantes do carcinoma papilífero de tiróide

Lima

Filho

Almeida

et al. 2003

Arq Bras Endocrinol Metab

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RESUMOIntrodução e Objetivos: Muitos estudos têm demonstrado possível relação entre a expressão de oncogenes e a agressividade histológica dos tumores tiroidianos. O presente trabalho investiga as alterações moleculares existentes nas variantes do carcinoma papilífero de tiróide (CPT), através da análise da expressão de proteínas relacionadas à tumorigênese, correlacionando-a com o prognóstico. Metodologia: 32 casos estudados de CPT foram selecionados de peças cirúrgicas, entre 1987 e 2000, sendo 5 homens e 27 mulheres com idades médias de 52,6 e 46,5 anos, respectivamente. Foram estudados anticorpos monoclonais anti-MIB-1, p53, c-erb-B2, bcl-2 e receptores de TSH e TGFβ. Resultados: Dos casos analisados, 11 foram considerados de melhor prognóstico (variantes microcarcinoma e encapsulado) e apresentaram elevada expressão de TSHR2 e TGFβR2 (100%), bcl-2 (81,8%), c-erb-B2 (90,9%) e menor expressão de p53 e MIB-1 (18,2%). Nos 13 casos classificados como de prognóstico intermediário (variantes clássica e folicular), a expressão de TSHR2 foi de 100%, TGFβR2 e bcl-2, 92,3%; c-erb-B2, 76,9%; p53, 23,1% e MIB-1, 69,2%. Finalmente, os 8 casos de pior prognóstico (varintes de células altas e de células colunares) mostraram expressão de TSHR2, bcl-2, c-erb-B2, em 100% dos casos, TGFβR2 em 87,5%, p53 em 75% e MIB-1 em 37,5%. Conclusão: As neoplasias mostraram-se bem diferenciadas em virtude da elevada expressão de TSHR2, TGFβR2, e baixa de p53. Em todos os grupos, a taxa proliferativa foi ausente ou baixa (<1,5%), com positividade maior nos tumores de prognóstico intermediário, sendo mais elevada (>1,5%) nos carcinomas de pior prognós-tico. Além disso, a positividade para a proteína bcl-2 foi progressivamente maior com a piora do prognóstico. Background and objectives: Studies investigating the molecular pathogenesis of common thyroid neoplasms have shown some association between oncogenes expression and histological aggressiveness of thyroid tumors. We have investigated molecular changes in variants of thyroid papillary carcinoma (TPC), by analyzing the expression of proteins related to its tumorigenesis, and further, its own relationship to the prognosis. Methods: We examined 32 surgical specimens of TPC obtained from 5 males and 27 females (mean ages of 52.6 and 46.5 years, respectively). Monoclonal antibodies anti-MIB-1, p53, c-erb-B2, TSH receptors, TGFβ receptors and bcl-2 were detected by immunohistochemistry. Results: 11 of the 32 cases had a better prognosis (microcarcinoma and encapsulated tumors), with high expression of TSHR2 and TGFβR2 (100%), bcl-2 (81.8%), c-erb-B2 (90.9%) and lesser expression of p53 and MIB-1 (18.2%). In the 13 cases with intermediate prognosis (classic and folicular), the expression of TSHR2 reached 100%; TGFβR2 and bcl-2, 92.3%; cerb-B2, 76.9%; p53, 23.1%; and MIB-1, 69.2%. The 8 cases with the worst

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“…Tanaka and coworkers (Tanaka et al 1997) studied TSHR protein expression in 21 PTCs (18 well differentiated) and 2 FTCs (both well differentiated) using IHC. They compared receptor immunostaining intensity and distribution to surrounding thyroid tissue.…”

Section: :6mentioning

confidence: 99%

Targeting the TSH receptor in thyroid cancer

Rowe¹,

Paul²,

Gedye³

et al. 2017

Endocrine-Related Cancer

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Recent advances in the arena of theranostics have necessitated a re-examining of previously established fields. The existing paradigm of therapeutic thyroid-stimulating hormone receptor (TSHR) targeting in the post-surgical management of differentiated thyroid cancer using levothyroxine and recombinant human thyroid-stimulating hormone (TSH) is well understood. However, in an era of personalized medicine, and with an increasing awareness of the risk profile of longstanding pharmacological hyperthyroidism, it is imperative clinicians understand the molecular basis and magnitude of benefit for individual patients. Furthermore, TSHR has been recently re-conceived as a selective target for residual metastatic thyroid cancer, with pilot data demonstrating effective targeting of nanoparticles to thyroid cancers using this receptor as a target. This review examines the evidence for TSHR signaling as an oncogenic pathway and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases. Priorities for further research are highlighted.

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Relationship between prognostic score and thyrotropin receptor (TSH-R) in papillary thyroid carcinoma: immunohistochemical detection of TSH-R

Cited by 31 publications

References 20 publications

Decreased expression of the thyroid-stimulating hormone receptor in poorly-differentiated carcinoma of the thyroid

Decreased expression of the thyroid-stimulating hormone receptor in poorly-differentiated carcinoma of the thyroid

Caracterização molecular das variantes do carcinoma papilífero de tiróide

Targeting the TSH receptor in thyroid cancer

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